A major challenge in treating infectious diseases is the duration of anti-infective therapy required to eradicate the infecting pathogen. Diseases like acute otitis media, urinary tract infections, and skin and skin-structure infections are often only effectively treated with anti-infective agents when the agents are administered for a number of days. Infections like endocarditis, bone and joint infections, and infections associated with biofilms can require many weeks of treatment, while tuberculosis and leprosy often require anti-infectives for several months, or more.
The major reason for the wide-range in therapy duration for different infectious diseases is the rate of pathogen replication. The nature of some pathogens is to replicate slowly while for others, their replication rate is environment dependent. Mycobacterium such as Mycobacterium tuberculosis and M. leprae replicate very slowly. The replication rate of staphylococci, streptococci and Gram-negative bacilli is rapid in some environments (e.g., lung parenchyma) but slow in other environments (e.g., within a biofilm or cardiac vegetation).
A large number of anti-infective agents are only active against a pathogen during replication. Therefore, for many of those pathogens that replicate slowly, a prolonged course of treatment is required to achieve complete eradication of the pathogen from the host.
Prolonged duration of anti-infective therapy increases the patient's risk of drug-related toxicity, increases the probability for drug-resistance selection, and decreases the likelihood that a patient will receive a complete course of therapy. Each of these outcomes can have profound societal costs, not only in terms of increased patient morbidity and mortality, but also in the increased consumption of scarce healthcare resources. Therefore, there is an urgent need for means of achieving treatment of infectious diseases that typically require a long duration of anti-infective therapy, while at the same time decreasing treatment duration.